Hydroxychloroquine (HCQ) is an antimalarial drug used as chemoprophylaxis against malaria caused byPlasmodium vivax in the Republic of Korea Army (ROKA). In this study, we evaluated the pharmacokinetics (PK) of HCQ and its metabolites and the relationship between the PK of HCQ and the effect of treatment of HCQ on vivax malaria in South Koreans. Three PK studies of HCQ were conducted with 91 healthy subjects and patients with vivax malaria. Plasma concentrations were analyzed by noncompartmental and mixed-effect modeling approaches. A two-compartment model with first-order absorption best described the data. The clearance and the central and peripheral volumes of distribution were 15.5 liters/h, 733 liters, and 1,630 liters, respectively. We measured the plasma concentrations of HCQ in patients with prophylactic failure of HCQ and compared them with the prediction intervals of the simulated concentrations for HCQ from the final PK model built in this study. In 71% of the patients with prophylactic failure, the plasma concentrations of HCQ were below the lower bounds of the 95% prediction interval, while only 8% of them showed higher levels than the upper bounds of the 95% prediction interval. We report that a significant cause of prophylactic failure among the individuals in ROKA was ascribed to plasma concentrations of HCQ lower than those predicted by the PK model. However, prophylactic failure despite sufficient plasma concentrations of HCQ was confirmed in several individuals, warranting continued surveillance to monitor changes in the HCQ susceptibility of Plasmodium vivax in the Republic of Korea.

Background: Climate change may affect Plasmodium vivax malaria transmission in a wide region including both subtropical and temperate areas.Objectives: We aimed to estimate the effects of climatic variables on the transmission of P. vivax in temperate regions.Methods: We estimated the effects of climatic factors on P. vivax malaria transmission using data on weekly numbers of malaria cases for the years 2001–2009 in the Republic of Korea. Generalized linear Poisson models and distributed lag nonlinear models (DLNM) were adopted to estimate the effects of temperature, relative humidity, temperature fluctuation, duration of sunshine, and rainfall on malaria transmission while adjusting for seasonal variation, between-year variation, and other climatic factors.Results: A 1°C increase in temperature was associated with a 17.7% [95% confidence interval (CI): 16.9, 18.6%] increase in malaria incidence after a 3-week lag, a 10% rise in relative humidity was associated with 40.7% (95% CI: –44.3, –36.9%) decrease in malaria after a 7-week lag, a 1°C increase in the diurnal temperature range was associated with a 24.1% (95% CI: –26.7, –21.4%) decrease in malaria after a 7-week lag, and a 10-hr increase in sunshine per week was associated with a 5.1% (95% CI: –8.4, –1.7%) decrease in malaria after a 2-week lag. The cumulative relative risk for a 10-mm increase in rainfall (≤ 350 mm) on P. vivax malaria was 3.61 (95% CI: 1.69, 7.72) based on a DLNM with a 10-week maximum lag.Conclusions: Our findings suggest that malaria transmission in temperate areas is highly dependent on climate factors. In addition, lagged estimates of the effect of rainfall on malaria are consistent with the time necessary for mosquito development and P. vivax incubation.

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The Republic of Korea experienced a re-emergence of Plasmodium vivax malaria in 1993. The incidence of this disease increased rapidly through 2000 with its geographic distribution expanding from the vicinity near the Demilitarized Zone to the adjacent outlying areas. However, the number of cases of P. vivax malaria since that time period has decreased. A total of 2,538 cases occurred in 2001, and this decreased to 1,761 cases and 1,164 cases in the two subsequent years. A total of 5,463 cases of P. vivax malaria were reported from 2001 through 2003; 25.26% (1,380) were reported among Republic of Korea military personnel, 27.48% (1,501) were among veterans who had been discharged from the military within two years, and 47.26% (2,582) were among the civilian population. Mosquito control activities by the North Korean and South Korean governments, chemoprophylaxis of Republic of Korea Army personnel, and the low level of Anopheles mosquitoes in 2001 may have been factors responsible for the decreasing number of malaria cases. However, local transmission might have taken place in urban regions of the malaria-risk areas that are within 30 km south of the Demilitarized Zone. Extensive intervention and continued surveillance are warranted to prevent the epidemic from re-expanding and to eliminate this disease in the Republic of Korea.

We expressed a protein in Saccharomyces cerevisiae in order to evaluate the humoral immune responses to the C-terminal region of the merozoite surface protein 1 of Plasmodium vivax. This protein (Pv200 18 ) had a molecular mass of 18 kDa and was reactive with the sera of individuals with patent vivax malaria on immunoblotting analysis. The levels of immunoglobulin M (IgM) and IgG antibodies against Pv200 18 were measured in 421 patients with vivax malaria (patient group), 528 healthy individuals from areas of nonendemicity (control group 1), and 470 healthy individuals from areas of endemicity (control group 2), using the indirect enzyme-linked immunosorbent assay (ELISA) method. To study the longevity of the antibodies, 20 subjects from the patient group were also tested for the antibody levels once a month for 1 year. When the cutoff values for seropositivity were determined as the mean ؉ 3 ؋ standard deviation of the antibody levels in control group 1, both IgG and IgM antibody levels were negative in 98.5% (465 of 472) of control group 2. The IgG and IgM antibodies were positive in 88.1% (371 of 421) and 94.5% (398 of 421) of the patient group, respectively. The IgM antibody became negative 2 to 4 months after the onset of symptoms, whereas the IgG antibody usually remained positive for more than 5 months. In conclusion, indirect ELISA using Pv200 18 expressed in S. cerevisiae may be a useful diagnostic method for vivax malaria.